title: The expanding role of yeast in cancer research and diagnosis: insights into the function of the oncosuppressors p53 and BRCA1/2.
abstract: When the glucose supply is high, despite the presence of oxygen, Saccharomyces cerevisiae uses fermentation as its main metabolic pathway and switches to oxidative metabolism only when this carbon source is limited. There are similarities between glucose-induced repression of oxidative metabolism of yeast and metabolic reprogramming of tumor cells. The glucose-induced repression of oxidative metabolism is regulated by oncogene homologues in yeast, such as RAS and Sch9p, the yeast homologue of Akt. Yeast also undergoes an apoptosis-like programmed cell death process sharing several features with mammalian apoptosis, including oxidative stress and a major role played by mitochondria. Evasion of apoptosis and sustained proliferative signaling are hallmarks of cancer. This, together with the possibility of heterologous expression of human genes in yeast, has allowed new insights to be obtained into the function of mammalian oncogenes/oncosuppressors. Here, we elaborate on the similarities between tumor and yeast cells underpinning the use of this model organism in cancer research. We also review the achievements obtained through heterologous expression in yeast of p53, BRCA1, and BRCA2, which are among the best-known cancer-susceptibility genes, with the aim of understanding their role in tumorigenesis. Yeast-cell-based functional assays for cancer genetic testing will also be dealt with.
authors.affiliation: Institute of Biomembranes and Bioenergetics, CNR, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Guaragnella
authors.forename: Vanessa
authors.initials: V
authors.lastname: Palermo
authors.forename: Alvaro
authors.initials: A
authors.lastname: Galli
authors.forename: Loredana
authors.initials: L
authors.lastname: Moro
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzoni
authors.forename: Sergio
authors.initials: S
authors.lastname: Giannattasio
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008954:Models, Biological; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53
keywords: BRCA1/2; cancer; mitochondria; p53; programmed cell death; yeast